High-intensity swimming alleviates nociception and neuroinflammation in a mouse model of chronic post-ischemia pain by activating the resolvin E1-chemerin receptor 23 axis in the spinal cord.

Abstract

Physical exercise effectively alleviates chronic pain associated with complex regional pain syndrome type-I. However, the mechanism of exercise-induced analgesia has not been clarified. Recent studies have shown that the specialized pro-resolving lipid mediator resolvin E1 promotes relief of pathologic pain by binding to chemerin receptor 23 in the nervous system. However, whether the resolvin E1-chemerin receptor 23 axis is involved in exercise-induced analgesia in complex regional pain syndrome type-I has not been demonstrated. In the present study, a mouse model of chronic post-ischemia pain was established to mimic complex regional pain syndrome type-I and subjected to an intervention involving swimming at different intensities. Chronic pain was reduced only in mice that engaged in high-intensity swimming. The resolvin E1-chemerin receptor 23 axis was clearly downregulated in the spinal cord of mice with chronic pain, while high-intensity swimming restored expression of resolvin E1 and chemerin receptor 23. Finally, shRNA-mediated silencing of chemerin receptor 23 in the spinal cord reversed the analgesic effect of high-intensity swimming exercise on chronic post-ischemic pain and the anti-inflammatory polarization of microglia in the dorsal horn of the spinal cord. These findings suggest that high-intensity swimming can decrease chronic pain via the endogenous resolvin E1-chemerin receptor 23 axis in the spinal cord.